Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer (NCT03693170), a na phase 2 study. The primary outcome is Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments.

2. Clinical Question

The registry describes the study purpose as evaluating the efficacy and safety of the three-drug combination in patients with BRAF V600-mutant metastatic colorectal cancer who had not received prior treatment for their metastatic disease. The primary endpoint’s population description is more specific: it refers to centrally confirmed BRAFV600E mutation and defines the Efficacy Set in terms of treatment exposure and mutation confirmation.

This is a single-group question: the endpoint describes responses among participants receiving the regimen, rather than an estimated difference between two assigned treatments. Without a comparator group, the study cannot isolate how much of the observed response pattern is attributable to the regimen relative to another treatment or to the course of disease without it. The registry record does not report a numerical cORR result, so the size and precision of the response estimate cannot be assessed from the posted primary outcome information.

3. Trial Design

This was a phase II, open-label, multicenter, single-group study. The listed arm received encorafenib plus binimetinib plus cetuximab. The registry records masking as none and allocation as not applicable, consistent with the absence of a randomized comparator arm. Enrollment was 95.

The study is marked completed. The recorded study start date is 2019-01-17, and the primary completion date is 2020-06-29. These dates describe the registry record’s study milestones; they do not, by themselves, indicate when every participant began or finished treatment.

The registry identifies the condition as BRAF V600E-mutant metastatic colorectal cancer. The study’s brief description refers to patients with BRAF V600 mutant metastatic colorectal cancer who had not received prior treatment for their metastatic disease. The primary endpoint description specifies a centrally confirmed BRAFV600E mutation for inclusion in the Efficacy Set and says that participants must have received at least one dose of study treatment. The number meeting that endpoint population definition is not reported in the registry record.

Open-label means treatment masking was not used, as also recorded directly in the registry. This design can describe outcomes in the treated group, but it does not offer a concurrent control group for separating treatment-associated outcomes from other influences. The record lists 14 outcome measures and one analysis. It does not report enough detail to establish the full statistical analysis plan, the timing of every assessment, or how the listed outcomes were prioritized beyond the primary endpoint designation.

The listed secondary outcomes include response rates assessed by central and local review, duration and time to response, and progression-free survival assessed by local review. Their presence indicates that the study registered additional outcome questions, but the registry information available for this analysis does not provide numerical results for those endpoints.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 125 subjects were screened for inclusion in the study. 30 subjects were excluded (29 due to eligibility criteria not met and 1 due to adverse event).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments, measured over From initiation of treatment to disease progression up to a maximum of 17.6 months..

The primary endpoint is confirmed overall response rate (cORR) based on local tumor assessments. It is defined as the percentage of confirmed responses, with a response comprising either a complete response (CR) or partial response (PR), according to the registry’s description of RECIST criteria. Local radiologist or investigator review was used for the primary assessment.

In general, an overall response endpoint captures whether tumors meet prespecified criteria for substantial shrinkage or disappearance. Confirmation requires that an initial response be verified, rather than counted from a single assessment alone. The registry describes CR as disappearance of all target lesions and PR as at least a 30% decrease in the sum of target-lesion diameters relative to the baseline sum. It also states that overall response combines CR and PR. The endpoint description refers to RECIST 1.1, while its further criterion text refers to RECIST v1.0; the registry record does not clarify this difference.

A response rate is a proportion, not a time-to-event measure. It can summarize the share of the defined population meeting response criteria during the assessment period, but it does not by itself describe how long response lasts or how long participants remain free of progression. The registry gives the primary endpoint timeframe as from treatment initiation to disease progression, up to a maximum of 17.6 months.

The endpoint’s numerical response rate, response count, denominator, and 95% confidence interval are not reported in the registry record. Consequently, the endpoint definition is available, but its estimated value and statistical precision cannot be described from the posted primary outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a proportion: the percentage of the endpoint population with a confirmed complete or partial response. In general, a proportion is formed by counting participants who meet a defined event criterion and relating that count to a clearly defined population. For this study, the registry specifies the response criterion and describes the Efficacy Set, but it does not report the numerator or denominator for the primary result. Without both, the cORR cannot be reconstructed from the registry information.

What does a confidence interval convey?

In general, a confidence interval gives a range of values compatible with the data under the method’s assumptions. It is used to show uncertainty around an estimate, rather than to guarantee that the true value lies in a particular range. A confidence interval around a response proportion helps readers judge how precisely that proportion has been estimated. The registry identifies a 95% confidence interval for the primary endpoint, but its limits are not reported in the registry record. Its width, position, and relation to any reference value therefore cannot be assessed.

Why does the analysis population matter?

The population used in an analysis determines who contributes to the estimate. The registry defines the Efficacy Set as included participants who received at least one dose of treatment and had a centrally confirmed BRAFV600E mutation. This is a specific analysis population, not automatically equivalent to everyone enrolled. Enrollment was 95, but the size of the Efficacy Set is not reported. Using enrollment as though it were the primary endpoint denominator could misstate the response proportion if the endpoint population differed.

The description also distinguishes central mutation confirmation from local tumor assessment. Mutation status helps define the endpoint population, while local radiologist or investigator review determines the primary response assessment. These are separate processes and should not be conflated. The registry additionally lists central tumor-assessment response outcomes, but does not report numerical results for either central or local response in the information.

What does the single-group design allow?

In general, a single-group study estimates outcomes in participants receiving the study regimen, without a concurrent randomized group receiving a comparator. Such an estimate can be informative descriptively, but it does not directly estimate a between-group treatment contrast. Differences in patient characteristics, care, assessment, or time can complicate comparisons with results from other studies. The registry records no allocation and no masking, and identifies a single-group model. Thus, a comparative effect estimate cannot be obtained from the primary endpoint as registered.

Open-label assessment means treatment assignment was not masked. For an outcome based on tumor review, knowledge of treatment can be relevant to how assessments are conducted or interpreted. Central review can offer a distinct assessment process, but the primary endpoint is explicitly based on local assessment. The record does not provide enough detail to characterize reviewer procedures, adjudication, or any planned comparison of local and central assessments.

What do the response criteria mean?

In general, RECIST provides standardized rules for classifying tumor response using measurements of target lesions and other disease findings. The registry defines a complete response as disappearance of all target lesions and a partial response as at least a 30% decrease in the sum of target-lesion diameters relative to baseline. It defines overall response as CR plus PR and says responses are confirmed. The description references RECIST 1.1 and later refers to RECIST v1.0 in its criteria text. The registry record does not explain the differing version references, so the exact version applied cannot be resolved from that description alone.

Response rate is distinct from duration of response, time to response and progression-free survival. In general, response rate records whether a participant meets response criteria; duration of response concerns how long a response persists; time to response concerns the interval until response; and progression-free survival concerns time until progression or another defined event. The registry lists these as separate outcomes, including local and central assessment variants for some. Their numerical values and analysis details are not reported in the registry record.

What analysis details remain unclear?

The record lists one analysis, but does not report the statistical method used to calculate the primary estimate or its interval. It does not report a detailed analysis plan, handling of missing assessments, rules for confirmation, or the number of participants excluded from the Efficacy Set. These details matter because they can influence which observations enter the estimate and how uncertainty is quantified. General statistical explanations cannot fill those record-specific gaps.

The registry’s primary endpoint timeframe is from treatment initiation to disease progression, up to a maximum of 17.6 months. This indicates the stated observation window for the endpoint, but the actual follow-up duration for individual participants and the timing of response assessments are not reported in the registry record. The stated endpoint timeframe should therefore not be interpreted as a common follow-up duration for all participants.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, including the primary confirmed overall response rate based on local assessment and secondary response, duration, time-to-response and progression-free-survival outcomes. When a study evaluates several outcomes, multiplicity can arise because testing or interpreting many results increases the chance of an apparently notable finding occurring by chance. In general, a prespecified strategy can address this issue, for example by identifying a hierarchy of outcomes or an adjustment method. The registry record does not report whether such a strategy was used, so no adjustment procedure or control of overall type I error should be assumed.

The record identifies one analysis, but this does not reveal the complete statistical analysis plan. The method for estimating the primary response rate and its confidence interval, and any planned sensitivity analyses, are not reported in the registry record. The existence of a listed analysis is not enough to determine how the multiple registered outcomes were handled.

The Efficacy Set is defined as included participants who received at least one dose of treatment and had a centrally confirmed BRAFV600E mutation. Its size is not reported. The number enrolled was 95, but the record does not establish that all enrolled participants contributed to the primary endpoint analysis. Reasons for exclusion, treatment exposure details beyond the at-least-one-dose definition, and the handling of participants without an evaluable assessment are not reported in the registry record.

Missing-data handling is also not reported in the registry record. It is therefore unclear how absent, incomplete, or unevaluable tumor assessments were treated in the cORR estimate. In general, these choices can affect both the estimate and its uncertainty, particularly when the analysis population and outcome denominator depend on evaluability. No particular missing-data assumption or imputation method can be attributed to this study from the registered information.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: large intestinal obstruction (6.3%), acute kidney injury (6.3%), intestinal obstruction (5.3%), nausea (5.3%), abdominal pain (4.2%).

The registry records 95 participants at risk for serious adverse events and 49 affected, and 95 at risk for other adverse events and 93 affected. These are counts of participants, not event rates over person-time. The record also lists 27 deaths. These figures describe safety reporting in the study group; they do not, on their own, establish whether an event or death was caused by the study regimen.

The serious adverse event terms with the listed percentages are large intestinal obstruction, 6.3%; acute kidney injury, 6.3%; intestinal obstruction, 5.3%; nausea, 5.3%; abdominal pain, 4.2%; and diarrhoea, 4.2%. These are registry-listed terms and percentages. They should not be added together: participants may have experienced more than one event, and the registry record does not specify whether categories overlap. Nor should the list be read as an exhaustive account of all safety events.

In general, a serious adverse event is a safety classification distinct from the ordinary notion of symptom severity. The record does not provide enough detail to characterize event duration, timing, management, or relationship to treatment. The death count is likewise not accompanied by a stated causal assessment in the figures. These counts provide a descriptive safety snapshot, not a comparison with another treatment group or a causal estimate.

12. What the Result Does, and Does Not, Mean

The registry record establishes that a phase II, open-label, single-group study evaluated encorafenib, binimetinib and cetuximab in previously untreated BRAF V600E-mutant metastatic colorectal cancer. It specifies confirmed overall response rate based on local tumor assessments as the primary endpoint and defines the response categories. It also reports enrollment and selected safety counts. However, the numerical primary response result and its confidence interval are not reported in the registry record. The central efficacy finding therefore cannot be quantified from the available registry information.

A response endpoint can describe the share of an analysis population meeting prespecified tumor-response criteria during the stated assessment period. It does not, by itself, show how long responses lasted, how outcomes compared with another treatment, or what would have happened without the regimen. The registry lists duration of response, time to response and progression-free survival as other outcomes, but their numerical results are not reported in the registry information.

The single-group design is important to interpretation. Without a randomized comparator, the study does not estimate a between-treatment difference. The open-label design and use of local review for the primary endpoint are also features to consider when assessing the endpoint. The registry record does not provide the numerical response estimate, assessment-level data, or detailed analysis information needed to evaluate the effect of these features on the reported result.

The safety counts indicate that adverse events were recorded among participants, including 49 participants with serious adverse events and 93 with other adverse events, each among 95 at risk. The record also lists 27 deaths and several serious adverse event terms with percentages. These observations should be read descriptively. The figures alone do not establish causation, comparative risk, or the clinical significance of each event for an individual participant.

In general, a registry record supports interpretation only to the extent that it reports the outcome values, analysis population, methods and uncertainty. In this case, important primary efficacy values and several analysis details are absent. The registered endpoint and design can be described, but a quantitative conclusion about the response estimate or its precision cannot be drawn from the posted results.

13. Why This Trial Matters Statistically

This study raises several important statistical interpretation issues because its primary outcome is a proportion from a single-group phase II design. The registry defines the outcome and the analysis population, but does not report the response count, denominator, estimated cORR or confidence interval. Without those quantities, readers cannot assess either the observed response frequency or the precision of the estimate. The gap illustrates why reporting an endpoint definition is not a substitute for reporting its result.

The distinction between enrollment and analysis population is also important. Although enrollment was 95, the Efficacy Set required at least one dose of study treatment and centrally confirmed BRAFV600E mutation. The size of that set is not reported. Transparent reporting of the analyzed population and denominator is essential for interpreting any proportion, because the estimate depends on who was included and how unevaluable cases were handled.

The study’s design sets limits on the estimand. A single-group response rate is descriptive of participants in that group; it is not a randomized comparison and cannot directly estimate a contrast against another regimen. Open-label treatment and local response assessment are further relevant context. The registry lists central-assessment response outcomes as well, but does not report their values or explain how local and central assessments relate analytically.

Multiplicity and missing-data practices matter when a record includes numerous outcomes and an endpoint population based on treatment exposure and mutation confirmation. The record lists 14 outcome measures, yet does not describe an adjustment strategy or missing-assessment handling. Those omissions make it difficult to determine how outcome selection, analysis choices, or incomplete assessments may affect interpretation.

Finally, safety counts and efficacy outcomes should remain distinct. The registry’s serious adverse event counts and death count are descriptive and are not a randomized comparative safety estimate. Clear statistical interpretation requires the outcome estimate, its uncertainty, the analyzed population and the analysis rules; several of these elements are not reported in the registry record.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpreting efficacy is that the registry record does not report the numerical primary endpoint result. The response count, analysis denominator, cORR estimate and 95% confidence-interval limits are absent. The endpoint can be described, but its magnitude and precision cannot be assessed. The Efficacy Set is defined, yet its size is not reported, so enrollment of 95 should not be treated as the primary analysis denominator.

The study was single-group, open-label and had no randomized comparator. The results therefore cannot provide a randomized estimate of comparative efficacy or safety. The primary endpoint relied on local radiologist or investigator assessment, while the registry also lists response outcomes based on central review. Numerical outcomes for these assessment approaches are not reported, and the record does not explain their relationship or any adjudication procedures.

The endpoint description refers to RECIST 1.1, while its detailed criteria text refers to RECIST v1.0. The registry record does not resolve this difference. It also does not report detailed assessment schedules, response-confirmation procedures, participant-level follow-up, or the statistical method used for the primary confidence interval. Although the timeframe is stated as from treatment initiation to disease progression up to a maximum of 17.6 months, the record does not provide individual follow-up information.

Multiplicity handling, missing-data methods, sensitivity analyses, and the number of participants excluded from the Efficacy Set are not reported in the registry record. Safety information is also limited for causal interpretation: counts and selected serious adverse event terms are available, but the described figures do not state whether events or deaths were considered related to treatment. These limitations constrain interpretation of both efficacy and safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer — NCT03693170.
• Registry record last updated 2026-07-16; status last verified 2026-06.
• Results first posted 2022-08-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03693170 is a completed phase II, open-label, multicenter, single-group study of encorafenib, binimetinib and cetuximab in previously untreated BRAF V600E-mutant metastatic colorectal cancer. Enrollment was 95. The recorded start date was 2019-01-17, and the primary completion date was 2020-06-29.

The primary endpoint was confirmed overall response rate based on local tumor assessments, defined as the percentage of confirmed complete or partial responses. The registry specifies a 95% confidence interval but does not report the numerical response estimate, response count, endpoint denominator, or interval limits. The Efficacy Set required at least one dose of treatment and centrally confirmed BRAFV600E mutation; its size is not reported.

The registry records 49 participants with serious adverse events and 93 with other adverse events, each among 95 at risk, and lists 27 deaths. These descriptive figures do not establish treatment causation or provide a randomized comparison.